SPECT imaging of interleukin-6 receptor in ovarian tumor xenografts with a novel radiotracer of 99mTc-HYNIC-Aca-LSLITRL

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• 作者：Fei Li ; Zhenzhong Zhang ; Teng Cheng ; Rui Wei ; Yun Dai ; Mengqin Lv…
• 关键词：Interleukin ; 6 receptor ; Ovarian cancer ; 99mTc ; HYNIC ; Aca ; LSLITRL ; 99mTc ; HYNIC ; Aca ; TLQASIL ; Molecular imaging
• 刊名：Amino Acids
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：48
• 期：1
• 页码：91-101
• 全文大小：1,426 KB
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• 作者单位：Fei Li (1)
  Zhenzhong Zhang (1)
  Teng Cheng (1)
  Rui Wei (1)
  Yun Dai (1)
  Mengqin Lv (1)
  Danfeng Luo (1)
  Xiaohua Zhu (2)
  Ding Ma (1)
  Ling Xi (1)
  Qingjian Dong (2)
  Xiangyi Ma (1)
  
  1. Molecular Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People’s Republic of China
  2. Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People’s Republic of China
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Analytical Chemistry
  Biochemical Engineering
  Life Sciences
  Proteomics
  Neurobiology
  
• 出版者：Springer Wien
• ISSN：1438-2199

文摘

Growing evidences have shown that the IL-6/IL-6R signal pathway promotes the tumor growth, angiogenesis, invasion and migration in various cancers, especially for epithelial ovarian cancer. Hence, including anti-IL-6 antibody (Siltuximab) and anti-IL-6R antibody (Tocilizumab), more and more therapeutic drugs targeting IL-6/IL-6R pathway were developed to block their activity. The molecular imaging of IL-6R is a significant factor for predicting tumor response to IL-6/IL-6R targeted drugs. However, few probes targeting IL-6R were designed and used for the specific detection. The purpose of this study was to develop and evaluate a novel radiotracer, 99mTc-HYNIC-Aca-LSLITRL, for SPECT imaging of interleukin-6 receptor. The expression of IL-6R was determined by western blot, immunofluorescence and immunohistochemistry. HYNIC-Aca-LSLITRL and HYNIC-Aca-TLQASIL were synthesized, and then were labeled with 99mTc. The stability and the cell-binding assay were performed. Ovarian tumor xenografts were established and subjected to SPECT imaging after injection of these two radiopharmaceuticals with or without excess primary peptides. The biodistribution of these two radiotracers was performed in nude mice bearing C13K tumors. 99mTc-HYNIC-Aca-LSLITRL and 99mTc-HYNIC-Aca-TLQASIL were obtained in >95 % labeling yield with favorably stability. In vitro studies demonstrated that the interleukin-6 receptor was overexpressed in ovarian cancer C13K cells. The SPECT imaging of interleukin-6 receptor and biodistribution studies showed that 99mTc-HYNIC-Aca-LSLITRL had higher tumor uptake and significantly lower kidney accumulation compared to 99mTc-HYNIC-Aca-TLQASIL. 99mTc-HYNIC-Aca-LSLITRL could be a promising agent for SPECT imaging of interleukin-6 receptor of ovarian cancer especially for those anti-IL-6R drugs under clinical trials, such as tocilizumab. Keywords Interleukin-6 receptor Ovarian cancer 99mTc-HYNIC-Aca-LSLITRL 99mTc-HYNIC-Aca-TLQASIL Molecular imaging